“…ICC can also become apparent over time and be confirmed with genetic testing (Fig. 1 ; [ 4 , 9 , 28 ]). Fig.…”
Section: Idiopathic Ventricular Fibrillation: Is It a Time- And Clini...mentioning
confidence: 86%
“…Unfortunately, in daily clinical practice, the required comprehensive clinical work-up of SCA survivors seems to be difficult. Indeed, less than one in five of these patients ultimately received complete cardiological work-up [ 9 , 29 ], which increases the chance of erroneously labelling those patients as having IVF. However, even when cardiological work-up has been completed, ICC can still be missed due to its rarity.…”
Section: Idiopathic Ventricular Fibrillation: Is It a Time- And Clini...mentioning
confidence: 99%
“…Percentages were calculated from pooled data of IVF patients previously described [ 4 , 9 , 10 , 13 , 17 , 28 ]. Change in diagnosis was calculated per group (clinical diagnosis and genetic diagnosis) and calculated as a percentage of the whole group of IVF patients n = 1207, respectively: n = 63 [ 13 ], n = 107 [ 28 ], n = 375 [ 17 ], n = 11 [ 4 ], n = 228 [ 10 ], n = 423 (of whom n = 367 received genetic testing); NB data from Supplementary Table 3 were used to calculate genetic cause: for arrhythmogenic right ventricular dysplasia (ARVD): PLN and PKP2 , for DCM: LMNA and TTN , for HCM: MYH7 and MYL2 , for Brugada syndrome: SCN5A , for CPVT: RYR2 , for LQTS: KCNQ1 [ 9 ]. With regard to DPP6*: this data is derived from patients living in a specific region in the Netherlands with high prevalence of this founder variant.…”
Section: Idiopathic Ventricular Fibrillation: Is It a Time- And Clini...mentioning
confidence: 99%
“…Alternatively, these patients might have (likely) pathogenic variants in genes associated with VF without cardiac phenotype such as: CALM1 [ 15 ], IRX3 [ 12 ], the more recently identified loss-of-function RYR2 variants associated with calcium-release deficiency syndrome (CRDS) [ 22 ] or the Dutch DPP6 haplotype [ 1 ]. In a Dutch IVF cohort, the latter was shown to be the cause in 10% of genetically tested patients [ 9 ]. Importantly, when cardiological screening does not provide clues for the diagnosis of ICC in the patient, analysis of the family can be of help.…”
Section: Idiopathic Ventricular Fibrillation: Is It a Time- And Clini...mentioning
confidence: 99%
“…Genetic testing is mainly indicated in the case of suspicion of inherited cardiac conditions (ICC) after complete cardiological work-up [ 23 , 31 ]. However, clinical signs of ICC can be absent or missed (due to incomplete/misinterpreted cardiological test results), thereby wrongfully labelling patients as having IVF [ 4 , 5 , 9 , 16 , 29 ]. Since a diagnosis of ICC in IVF patients influences not only their own but also their family’s therapeutic options, one could argue that genetic testing should be more widely used in IVF patients.…”
Idiopathic ventricular fibrillation (IVF) is a diagnosis of exclusion in sudden cardiac arrest (SCA) survivors. Although there are clear guidelines on the clinical work-up of SCA survivors, less than one in five patients receives a complete work-up. This increases the chances of erroneously labelling these patients as having IVF, while 10–20% of them have an inherited cardiac condition (ICC). Diagnoses of ICC increase over time due to (additional) deep phenotyping or as a result of spontaneous expression of ICC over time. As SCA survivors can also harbor (likely) pathogenic variants in cardiomyopathy-associated genes in the absence of a phenotype, or can have another ICC without a clear cardiac phenotype, the question arises as to whether genetic testing in this group should be routinely performed. Family history (mainly in the case of sudden death) can increase suspicion of an ICC in an SCA victim, but does not add great value when adults underwent a complete cardiological work-up. The diagnosis of ICC has treatment consequences not only for the patient but also for their family. Genetic diagnostic yield does not appear to increase with larger gene panels, but variants of unknown significance (VUS) do. Although VUS can be confusing, careful and critical segregation analysis in the family can be performed when discussed in a multidisciplinary team at a center of expertise with at least a cardiologist as well as a clinical and laboratory geneticist, thereby degrading or promoting VUS. When to introduce genetic testing in SCA survivors remains a matter of debate, but the combination of quick, deep phenotyping with additional genetic testing for the unidentifiable phenotypes, especially in the young, seems preferable.
“…ICC can also become apparent over time and be confirmed with genetic testing (Fig. 1 ; [ 4 , 9 , 28 ]). Fig.…”
Section: Idiopathic Ventricular Fibrillation: Is It a Time- And Clini...mentioning
confidence: 86%
“…Unfortunately, in daily clinical practice, the required comprehensive clinical work-up of SCA survivors seems to be difficult. Indeed, less than one in five of these patients ultimately received complete cardiological work-up [ 9 , 29 ], which increases the chance of erroneously labelling those patients as having IVF. However, even when cardiological work-up has been completed, ICC can still be missed due to its rarity.…”
Section: Idiopathic Ventricular Fibrillation: Is It a Time- And Clini...mentioning
confidence: 99%
“…Percentages were calculated from pooled data of IVF patients previously described [ 4 , 9 , 10 , 13 , 17 , 28 ]. Change in diagnosis was calculated per group (clinical diagnosis and genetic diagnosis) and calculated as a percentage of the whole group of IVF patients n = 1207, respectively: n = 63 [ 13 ], n = 107 [ 28 ], n = 375 [ 17 ], n = 11 [ 4 ], n = 228 [ 10 ], n = 423 (of whom n = 367 received genetic testing); NB data from Supplementary Table 3 were used to calculate genetic cause: for arrhythmogenic right ventricular dysplasia (ARVD): PLN and PKP2 , for DCM: LMNA and TTN , for HCM: MYH7 and MYL2 , for Brugada syndrome: SCN5A , for CPVT: RYR2 , for LQTS: KCNQ1 [ 9 ]. With regard to DPP6*: this data is derived from patients living in a specific region in the Netherlands with high prevalence of this founder variant.…”
Section: Idiopathic Ventricular Fibrillation: Is It a Time- And Clini...mentioning
confidence: 99%
“…Alternatively, these patients might have (likely) pathogenic variants in genes associated with VF without cardiac phenotype such as: CALM1 [ 15 ], IRX3 [ 12 ], the more recently identified loss-of-function RYR2 variants associated with calcium-release deficiency syndrome (CRDS) [ 22 ] or the Dutch DPP6 haplotype [ 1 ]. In a Dutch IVF cohort, the latter was shown to be the cause in 10% of genetically tested patients [ 9 ]. Importantly, when cardiological screening does not provide clues for the diagnosis of ICC in the patient, analysis of the family can be of help.…”
Section: Idiopathic Ventricular Fibrillation: Is It a Time- And Clini...mentioning
confidence: 99%
“…Genetic testing is mainly indicated in the case of suspicion of inherited cardiac conditions (ICC) after complete cardiological work-up [ 23 , 31 ]. However, clinical signs of ICC can be absent or missed (due to incomplete/misinterpreted cardiological test results), thereby wrongfully labelling patients as having IVF [ 4 , 5 , 9 , 16 , 29 ]. Since a diagnosis of ICC in IVF patients influences not only their own but also their family’s therapeutic options, one could argue that genetic testing should be more widely used in IVF patients.…”
Idiopathic ventricular fibrillation (IVF) is a diagnosis of exclusion in sudden cardiac arrest (SCA) survivors. Although there are clear guidelines on the clinical work-up of SCA survivors, less than one in five patients receives a complete work-up. This increases the chances of erroneously labelling these patients as having IVF, while 10–20% of them have an inherited cardiac condition (ICC). Diagnoses of ICC increase over time due to (additional) deep phenotyping or as a result of spontaneous expression of ICC over time. As SCA survivors can also harbor (likely) pathogenic variants in cardiomyopathy-associated genes in the absence of a phenotype, or can have another ICC without a clear cardiac phenotype, the question arises as to whether genetic testing in this group should be routinely performed. Family history (mainly in the case of sudden death) can increase suspicion of an ICC in an SCA victim, but does not add great value when adults underwent a complete cardiological work-up. The diagnosis of ICC has treatment consequences not only for the patient but also for their family. Genetic diagnostic yield does not appear to increase with larger gene panels, but variants of unknown significance (VUS) do. Although VUS can be confusing, careful and critical segregation analysis in the family can be performed when discussed in a multidisciplinary team at a center of expertise with at least a cardiologist as well as a clinical and laboratory geneticist, thereby degrading or promoting VUS. When to introduce genetic testing in SCA survivors remains a matter of debate, but the combination of quick, deep phenotyping with additional genetic testing for the unidentifiable phenotypes, especially in the young, seems preferable.
Background
Idiopathic ventricular fibrillation (iVF) is a rare cause of sudden cardiac arrest and, by definition, a diagnosis of exclusion. Due to the rarity of the disease, previous and current studies are limited by their retrospective design and small patient numbers. Even though the incidence of iVF has declined owing to the identification of new disease entities, an important subgroup of patients remains.
Aim
To expand the existing Dutch iVF Registry into a large nationwide cohort of patients initially diagnosed with iVF, to reveal the underlying cause of iVF in these patients, and to improve arrhythmia management.
Methods
The Dutch iVF Registry includes sudden cardiac arrest survivors with an initial diagnosis of iVF. Clinical data and outcomes are collected. Outcomes include subsequent detection of a diagnosis other than ‘idiopathic’, arrhythmia recurrence and death. Non-invasive electrocardiographic imaging is used to investigate electropathological substrates and triggers of VF.
Results
To date, 432 patients have been included in the registry (median age at event 40 years (interquartile range 28–52)), 61% male. During a median follow-up of 6 (2–12) years, 38 patients (9%) received a diagnosis other than ‘idiopathic’. Eleven iVF patients were characterised with electrocardiographic imaging.
Conclusion
The Dutch iVF Registry is currently the largest of its kind worldwide. In this heterogeneous population of index patients, we aim to identify common functional denominators associated with iVF. With the implementation of non-invasive electrocardiographic imaging and other diagnostic modalities (e.g. echocardiographic deformation, cardiac magnetic resonance), we advance the possibilities to reveal pro-fibrillatory substrates.
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